The role of toll-like receptors in the regulation of neutrophil migration, activation, and apoptosis
The role of toll-like receptors in the regulation of neutrophil migration, activation, and apoptosis
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DOI：
10.1086/431992
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发表时间：
2005-11-15
影响因子：
11.8
通讯作者：
Whyte, MKB
中科院分区：
文献类型：
--
作者：
Sabroe, I;Dower, SK;Whyte, MKB
toll样受体（TLRs）在检测入侵病原体和诱导宿主抗微生物防御中起着至关重要的作用。TLR4是主要的内毒素受体，TLR2的激动剂主要来源于革兰氏阳性菌，可能在败血症的发病机制中起重要作用。TLR2和TLR4激动剂都能调节重要的中性粒细胞功能，包括粘附、活性氧的产生和趋化因子的释放，并激活主要的促炎信号通路，包括核因子- κ B通路。TLR刺激仅对中性粒细胞凋亡产生适度的直接抑制，尽管该信号因单核细胞的存在而被极大地放大，这表明TLR激动剂对中性粒细胞寿命的调节可能主要是由其他内毒素应答细胞的反应介导的。我们认为TLR对中性粒细胞的激活是高度调控的，允许急性中性粒细胞对TLR激活的抗菌反应，同时通过需要单个核细胞的存在来显着延长中性粒细胞的存活，从而“制动”炎症。
Toll-like receptors (TLRs) play an essential role in the detection of invading pathogens and in the induction of host antimicrobial defenses. TLR4, the major endotoxin receptor, and TLR2, with agonists derived principally from gram-positive organisms, are likely to be important in the pathogenesis of sepsis. Both TLR2 and TLR4 agonists regulate important neutrophil functions, including adhesion, generation of reactive oxygen species, and release of chemokines, and activate major proinflammatory signaling pathways, including the nuclear factor-kappa B pathway. TLR stimulation produces only a modest direct inhibition of neutrophil apoptosis, although this signal is greatly amplified by the presence of monocytes, suggesting that regulation of the life span of neutrophils by TLR agonists may be principally mediated by responses of other endotoxin-responsive cells. We suggest that activation of neutrophils by TLRs is highly regulated, permitting acute neutrophil antimicrobial responses to TLR activation while providing a "brake" on inflammation by requiring the presence of mononuclear cells to significantly extend neutrophil survival.